Deep learning models for predicting variant pathogenicity have not been thoroughly evaluated on real-world clinical phenotypes. Here, we apply state-of-the-art pathogenicity prediction models to hereditary breast cancer gene variants in UK Biobank participants. Model predictions for missense variants in BRCA1, BRCA2 and PALB2, but not ATM and CHEK2, were associated with breast cancer risk. However, deep learning models had limited clinical utility when specifically applied to variants of uncertain significance.
NPJ precision oncology. 2024 Oct 19*** epublish ***
Ryan D Chow, Katherine L Nathanson, Ravi B Parikh
Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA. ., Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Division of Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.